• Title, Summary, Keyword: VEGF-C

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VEGF-C and VEGF-D Expression and its Correlation with Lymph Node Metastasis in Esophageal Squamous Cell Cancer Tissue

  • Yang, Zeng;Wang, Yong-Gang;Su, Kai
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.271-274
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    • 2015
  • Background: To explore vascular endothelial growth factor C (VEGF-C) and VEGF-D expression and its correlation with lymph node metastasis in esophageal squamous cell cancer (ESCC) tissue. Materials and Methods: Immunohistochemical methods were applied to detect the levels of VEGF-C and VEGF-D expression in 64 surgicall removal ESCC tissues, tissues adjacent to cancer and normal tissues, and the relationship between VEGF-C and VEGF-D expression and lymph node metastasis was analyzed. Results: Both VEGF-C and VEGF-D were expressed by varying degrees in esophageal cancer tissue, the tissue adjacent to cancer and normal tissue, and the positive expression rate went down successively. The positive expression rates of VEGF-C (59.4%) and VEGF-D (43.8%) in esophageal cancer tissue were significantly higher than in the tissue adjacent to cancer (34.4%, 15.6%) and normal tissue (20.3%, 12.5%), respectively, in which significant differences were manifested (p<0.01). Positive expression rates of VEGF-C and VEGF-D in esophageal cancers with lymph node metastasis were markedly higher than without such metastasis (p<0.01), while those in the tissue with TNM staging I~II were markedly lower than that with TNM staging III~IV (p<0.01). Conclusions: Both VEGF-C and VEGF-D are highly expressed in ESCC tissue, which may be related to the lymph node metastasis of cancer cells. Hence, VEGF-C and VEGF-D can be clinically considered as important reference indexes of lymph node metastasis in esophageal cancer.

The Correlation between the Expression of E-cadherin, VEGF-C, VEGF-D and the Real Extent of Lymph Node Metastases using Cytokeratin 18 in Early Gastric Cancer (조기위암에서 E-cadherin, VEGF-C, VEGF-D의 발현과 Cytokeratin 18로 면역화학염색 한 림프절 전이와의 연관성)

  • Kim, Dae Hoon;Yun, Hyo Yung;Song, Young Jin;Ryu, Dong Hee;Min, In Choel;Sung, Rohyun;Lee, Sang Eok
    • Journal of Gastric Cancer
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    • v.8 no.2
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    • pp.70-78
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    • 2008
  • Purpose: VEGF-C and VEGF-D are angiogenetic factors, and abnormal expression of E-cadherin hasa role in the progression of gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of E-cadherin, VEGF-C and VEGF-D with the presence of lymph node metastases (LNM) using cytokeratin 18 in early gastric cancer (EGC). Materials and Methods: Immunohistochemical staining for E-cadherin, VEGF-C and VEGF-D was performed in 49 EGC patients from March 1997 to December 2002. To evaluate the real extent of LNM, 1,562 lymph nodes from 49 patients were re-examined with the use of cytokeratin 18. Results: Eleven (0.7%) LNM were newly found in 12.2% (n=6) of patients. The real LNM rate was 3.6% in mucosal invasive (m) cancer and 38.1% in submucosal invasive (sm). Stage migration was seen in three patients (6.1%). Abnormal expression of E-cadherin was detected in 36.7% of the patients and expression of VEGF-C and VEGF-D was detected in 16.3% and 36.7% of the patients, respectively. Abnormal expression of E-cadherin was significantly correlated with tumor differentiation (P=0.0103) and Lauren classification (P<0.0001). There was no positive relationship of VEGF-C and VEGF-D expression with the clinicopathological findings for EGC including LNM. However, the frequency of lymph node metastases was significantly higher in patients that demonstrated abnormal expression of E-cadherin with positive immunoreactivity of VEGF-C or VEGF-D (P=0.031). Conclusion: In present study, we could not demonstrate a relationship between the presence of LNM and expression of VEGF-C and VEGF-D in EGC. However, VEGF-C or VEGF-D expression, in addition to the abnormal expression of E-cadherin, was correlated with the real extent of LNM in EGC.

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GENE EXPRESSION FOR LYMPHANGIOGENIC FACTORS IN ORAL MUCOSAL SQUAMOUS CELL CARCINOMA (구강점막 편평상피세포암에서 림프관형성 유전자 발현)

  • Park, Young-Wook;Kim, Seong-Gon;Kim, So-Hee;Kim, Han-Seok;Kim, Min-Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.31 no.6
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    • pp.453-460
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    • 2009
  • Background and Purpose: Vascular endothelial growth factor (VEGF)-C, VEGF-D and their tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. Oral mucosal squamous cell carcinoma (OMSCC) easily metastasizes to cervical lymph nodes, so we determined the expression levels of VEGF-C, VEGF-D and VEGFR-3 in oral squamous cell carcinoma. Materials and Methods: We performed Western blot analyses with 4 OMSCC cultured tumor cell lines (SCC9, KB, YD-10B, YD-38), and with 7 surgical specimens of OMSCC for the detection of VEGF-C, VEGF-D and VEGFR-3 proteins. Expression of VEGF-C mRNA as well as mRNA for VEGFR-3 in 4 OMSCC cell lines (KB, SCC-4, SCC-9, YD-10B) was investigated by RT-PCR. We also measured VEGFC/VEGF-D protein concentrations in the media and protein concentration of VEGFR-3 in cell lysates of 4 OMSCC cell lines (SCC9, KB, YD-10B, YD-38) using commerical ELISA kits. Finally, we performed immunoprecipitation for the detection of VEGF-C in cell lysates of 4 OMSCC cells (KB, SCC-4, SCC-9, YD-10B) and real-time RT-PCR for the quantification of VEGF-C mRNA. Results: In the result of Western blotting with cell lysates of 4 OMSCC cells, we could not detect the protein expression of VEGF-C, VEGF-D, and VEGFR-3. But, all tumor tissues demonstrated VEGF-C and VEGFR-3. VEGF-C mRNA was detected at various levels in 4 OMSCC cell lines. Moreover, OMSCC cells secreted VEGF-C, not VEGF-D and VEGFR-3 was also detected in cell lysates of OMSCC by ELISA. Immunoprecipitation and real-time RT-PCR revealed VEGF-C was also expressed in 4 OMSCC cell lines. Conclusion: Taken together, tumor cells of OMSCC secrete VEGF-C, not VEGF-D. And VEGFR-3 is expressed tumor cells as well as OMSCC tumor tissues, needs further study.

Effects of Cyclooxygenase-2 Expression on Lymphangiogenesis and Lymph Node Metastasis in Gastric Cancer Tissues (위암조직에 있어 COX-2 발현이 림프관신생과 림프절 전이에 미치는 영향)

  • Chun, Hu-An;Paik, Seung-Sam;Song, Young-Soo;Kwon, Sung-Joon
    • Journal of Gastric Cancer
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    • v.6 no.4
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    • pp.284-290
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    • 2006
  • Purpose: Many previous studies have suggested that cyclooxygenase-2 (COX-2) over expression is closely related to angiogenesis. However, few have reported the relationship between COX-2 and lymphangiogenesis which is still unclear, The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenetic factor, VEGF-C, in human gastric cancer and to correlate COX-2 and VEGF-C expression with other clinocopathological features to investigate whether COX-2 contributes to lymphangiogenesis and enhances lymph node metastasis. Materials and Methods: One hundred patients who underwent curative radical surgery in Hanyang University hospital from July 1998 to June 2001 were selected. The expression of COX-2 and VEGF-C were detected by using immunohistochemistry, and the relationships between these two parameters and several clinicopathological factors (gender, stage, lymph node status, tumor location, Lauren classification and angioinvasion) were determined. Results: Increased COX-2 expression was found in 86 of 100 tumor samples (86%) and in 70 of 100 tumor samples (70%) with VEGF-C. A high correlation between VEGF-C expression and lymph node metastasis was observed (P=0.033) along as well as COX-2 expression (P=0.012). Also, there was a significant correlation between COX-2 and VEGF-C expression (P=0.026), yet no correlation were found between COX-2 and VEGF-C expression and other clinicopathological parameters. Conclusion: Our study suggests that COX-2 expression contributes to lymphangiogenesis by mediating VEGF-C and finally promoting lymph node metastasis.

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Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

  • Cho, Kyung-Ok;Kim, Joo Youn;Jeong, Kyoung Hoon;Lee, Mun-Yong;Kim, Seong Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.4
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    • pp.281-289
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    • 2019
  • Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

Clinical Significance of VEGF-C and COX-2 Expression in Gastric Carcinoma with Submucosal Invasion (점막하 침윤 조기위암 환자에서 VEGF-C와 COX-2 발현의 임상적 의의)

  • Cho, Yun-Jung;Lee, Jung-Uee;Lee, Kwan-Ju;Park, Cho-Hyun;Park, Seung-Man;Jeon, Hae-Myung;Ahn, Chang-Joon;Kim, Jeong-Goo;Lee, Dong-Ho;Lee, Sang-Chul
    • Journal of Gastric Cancer
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    • v.9 no.3
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    • pp.96-103
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    • 2009
  • Purpose: Lymph node metastasis is an important factor in determining prognosis and therapeutic options for early gastric cancer (EGC) patients. Vascular endothelial growth factor (VEGF)-C and D are known as lymphangiogenic factors, and cyclooxygenase (COX)-2 is thought to play a role in lymph node metastasis in gastric carcinoma. This study was designed to determine whether the expression of VEGF-C, VEGF-D, and COX-2 is associated with clinicopathologic factors, especially lymph node metastasis in EGCs invading the submucosa. Materials and Methods: Tissue samples were obtained from 85 Patients undergoing standard gastrectomy with lymph node dissection between 1991 and 2007 in the Department of Surgery of Daejeon St. Mary's Hospital in Daejeon, Korea. All patients were diagnosed with gastric cancers and submucosal invasion. We examined the expression of VEGF-C, VEGF-D, and COX-2 using immunohistochemical methods. Results: Of the 85 patients, 16 (18.8%) had lymph node metastasis. VEGF-C, VEGF-D, and COX-2 were positively expressed in 34.1% (29/85), 22.3% (19/85), and 37.6% (32/85) of the patients. VEGF-C and COX-2 expression was significantly correlated with lymph node metastasis (P<0.05). A positive correlation existed between VEGF-C and COX-2 expression (P< 0.001). Conclusion: VEGF-C and COX-2 expression is associated with lymph node metastasis in gastric cancer with submucosal invasion. VEGF-C and COX-2 may thus be predictive markers for lymph node metastasis in EGC patients with submucosal invasion.

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Immunohistochemical Study of C-erbB-2 and VEGF Expression in Non-Small Cell Lung Cancer (비소세포 폐암에서 C-erbB-2와 VEGF 발현에 대한 면역조직화학적 연구)

  • Shin, Jong Wook;Ha, Kyung Won;Choi, Jae Cheol;Kim, Jae Yeol;Park, In Whon;Choi, Byoung Whui;Yoo, Jae Hyung
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.1
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    • pp.43-50
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    • 2007
  • Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs.

5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

  • Wu, Wei-Qiang;Fauzee, Nilufer Jasmine Selimah;Wang, Ya-Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.991-994
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    • 2012
  • Objective: VEGF-C has recently been identified as a key molecule which is involved in tumor lymphangiogenesis. The aim of this research was to investigate the role of PARP-1 inhibition in the regulation of VEGF-C expression in CT26 cells. Methods: CT26 cells were treated with or without the PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ). The expression of PARP-1, NF-kB, and VEGF-C proteins in CT26 cells was measured by Western blot analysis and the VEGF-C mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). CT26-secreted VEGF-C was detected by enzyme-linked immunosorbent assay (ELISA). Results: The results of Western blot analysis showed that the expression levels of PARP-1, NF-kB, and VEGF-C were reduced in 5-AIQ treated CT26 cells and the levels of VEGF-C mRNA in 5-AIQ treated CT26 were significantly lower than t in 5-AIQ-untreated cells (P<0.05). The concentrations of CT26-secreted VEGF-C were also dramatically decreased (P<0.05). Conclusion: Here, we provide evidence for the first time that PARP-1 inhibition dramatically reduces VEGF-C expression via the nuclear factor NF-kB signaling pathway. We therefore propose that PARP-1 inhibition has an anti-lymphangiogenic effect and may contribute to the prevention of metastatic dissemination via the lymphatic system.

CD44v3 and VEGF-C Expression and its Relationship with Lymph Node Metastasis in Squamous Cell Carcinomas of the Uterine Cervix

  • Liu, Ye-Qing;Li, Hai-Feng;Han, Jing-Jing;Tang, Qiong-Lan;Sun, Qing;Huang, Zhi-Quan;Li, Hai-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.5049-5053
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    • 2014
  • Background: To investigate the expression of CD44v3 and vascular endothelial growth factor-C (VEGF-C) and their relationship with lymph node metastasis in squamous cell carcinomas (SCC) of the uterine cervix. Materials and Methods: Expression of CD44v3 and VEGF-C was analyzed in 109 cases of cervical SCC by immunohistochemistry (IHC). The relationship was analyzed between expression and the patient age, histological differentiation, formation of tumor emboli in lymphoid vessels, lymph node metastasis, FIGO staging, and TNM classification. Results: Expression rates for both CD44v3 and VEGF-C were 43.1% in cervical SCC. The cells with positive immunohistochemical staining of CD44v3 were distributed mainly around the keratin pearls in well differentiated carcinomas, but distributed diffusely in the moderately and poorly differentiated lesions. VEGF-C was found stained positively in most of the tumor cells. There were differences in expression between normal epithelium and atypical hyperplasia as well as carcinoma. Both CD44v3 and VEGF-C were found to be associated positively with lymph node metastasis and TNM classification (both p=0.000). Neither CD44v3 nor VEGF-C was found to be associated with patient age, histological differentiation, formation of tumor emboli in lymphoid vessels and FIGO staging. CD44v3 was found to be associated with VEGF-C positively (p=0.000). Conclusions: Abnormal expression of CD44v3 and VEGF-C is associated closely with the lymph node metastasis in cervical SCC, and these agents may cooperate in carcinogenesis and development of metastatic lesions.

The role of Purkinje cell-derived VEGF in cerebellar astrogliosis in Niemann-Pick type C mice

  • Park, Min Hee;Lee, Ju Youn;Jeong, Min Seock;Jang, Hyung Sup;Endo, Shogo;Bae, Jae-sung;Jin, Hee Kyung
    • BMB Reports
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    • v.51 no.2
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    • pp.79-84
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    • 2018
  • Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative disorder caused by a deficiency of NPC1 gene function, which leads to severe neuroinflammation such as astrogliosis. While reports demonstrating neuroinflammation are prevalent in NP-C, information about the onset and progression of cerebellar astrogliosis in this disorder is lacking. Using gene targeting, we generated vascular endothelial growth factor (VEGF) conditional null mutant mice. Deletion of VEGF in cerebellar Purkinje neurons (PNs) led to a significant increase of astrogliosis in the brain of NP-C mice in addition to the loss of PNs, suggesting PN-derived VEGF as an important factor in NP-C pathology. Moreover, replenishment of VEGF in neurons improved brain pathology in NP-C mice. Overall, our data provide a new pathological perspective on cerebellar astrogliosis in NP-C and suggest the importance of VEGF as a therapeutic target for this disease.